Jaundice in the Newborns - WHO newborn CC
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Jaundice in the Newborns
Jaundice is the most common morbidity in the first week of life, occurring in 60% of term and 80% of
preterm newborn. Jaundice is the most common cause of readmission after discharge from birth
hospitalization.1
Jaundice in neonates is visible in skin and eyes when total serum bilirubin (TSB) concentration exceeds 5
to 7 mg/dL. In contrast, adults have jaundice visible in eyes (but not in skin) when TSB concentration
exceeds 2 mg/dL. Increased TSB concentration in neonate results from varying contributions of three
factors namely increased production from degradation of red cells, decreased clearance by the
immature hepatic mechanisms and reabsoption by enterohepatic circulation (EHC).
High serum bilirubin levels carry a potential to cause neurological impairment with serious
consequences in a small fraction of jaundiced babies. In most cases, jaundice is benign and no
intervention is required. Approximately 5-10% of them have clinically significant jaundice that require
treatment to lower serum bilirubin levels in order to prevent neurotoxicity.
Physiological versus pathological jaundice
Jaundice attributable to physiological immaturity of neonates to handle increased bilirubin production is
termed as ‘physiological jaundice’. Visible jaundice usually appears between 24 to 72 hours of age. TSB
level usually rises in term infants to a peak level of 12 to 15 mg/dL by 3 days of age and then falls. In
preterm infants, the peak level occurs on the 3 to 7 days of age and TSB can rise over 15 mg/dL. It may
take weeks before the TSB levels falls under 2 mg/dL in both term and preterm infants.
‘Pathological jaundice’ is said to be present when TSB concentrations are not in ‘physiological jaundice’
range, which is defined arbitrarily and loosely as more than 5 mg/dL on first day, 10 mg/dL on second
day, and 12-13 mg/dL thereafter in term neonates.2 Any TSB value of 17 mg/dL or more should be
regarded as pathologic and should be evaluated for the cause, and possible intervention, such as
phototherapy.3
It may be noted that the differentiation between ‘pathological’ and ‘physiological’ is rather arbitrary,
and is not clearly defined. Presence of one or more of following conditions would qualify a neonate to
have pathological jaundice2:
1. Visible jaundice in first 24 hours of life. However slight jaundice on face at the end of first day
(say 18 to 24 hr) is common and can be considered physiological.
2. Presence of jaundice on arms and legs on day 2
3. Yellow palms and soles anytime
4. Serum bilirubin concentration increasing more than 0.2 mg/dL/hour or more than 5 mg/dL in 24
hours
5. If TSB concentration more than 95th centile as per age-specific bilirubin nomogram
6. Signs of acute bilirubin encephalopathy or kernicterus
7. Direct bilirubin more than 1.5 to 2 mg/dL at any age
8. Clinical jaundice persisting beyond 2 weeks in term and 3 weeks in preterm neonatesCauses of pathological jaundice
Common causes of pathological jaundice include:
1. Hemolysis: blood group incompatibility such as those of ABO, Rh and minor groups, enzyme
deficiencies such as G6PD deficiency, autoimmune hemolytic anemia
2. Decreased conjugation such as prematurity
3. Increased enterohepatic circulation such as lack of adequate enteral feeding that includes
insufficient breastfeeding or the infant not being fed because of illness, GI obstruction
4. Extravasated blood: cephalhematoma, extensive bruising etc
Clinical assessment of jaundice
The parents should be counselled regarding benign nature of jaundice in most neonates, and for
the need to be watchful and seek help if baby appears too yellow. The parents should be
explained about how to see for jaundice in babies (in natural light and without any yellow
background).
Visual inspection of jaundice (Panel 1) is believed to be unreliable, but if it is performed properly
(ie examining a naked baby in bright natural light and in absence of yellow background), it has
reasonable accuracy particularly when TSB is less than 12 to 14 mg/dL or so. Absence of
jaundice on visual inspection reliably excludes the jaundice. At higher TSBs, visual inspection is
unreliable and, therefore, TSB should be measured to ascertain the level of jaundice.4
All the neonates should be examined at every opportunity but not lesser than every 12 hr until
first 3 to 5 days of life for occurrence of jaundice. The babies being discharged from the hospital
at 48 to 72 hours should be seen again after 48 to 72 hours of discharge.
The neonates at higher risk of jaundice should be identified at birth and kept under enhanced
surveillance for occurrence and progression of jaundice. These infants include5:
o GestationPanel 1 Visual inspection of jaundice
1. Examine the baby in bright natural light. Alternatively, the baby can be examined in white
fluorescent light. Make sure there is no yellow or off white background.
2. Make sure the baby is naked.
3. Examine blanched skin and gums, and sclerae
4. Note the extent of jaundice (Kramer’s rule)6
o Face 5-7 mg/dL
o Chest 8-10 mg/dL
o Lower abdomen/thigh 12 -15 mg/dL
o Soles/Palms >15 mg/dL
5. Depth of jaundice (degree of yellowness) should be carefully noted as it is an important indicator
of level of jaundice and it does not figure out in Karmer’s rule.
A deep yellow staining (even in absence of yellow soles or palms) is often associated with sever
jaundice and therefore TSB should be estimated in such circumstances.
Measurement of serum bilirubin
1. Transcutaneus bilirubinometry (TcB)4
a. TcB is a useful adjunct to TSB measurement, and routine employment of TcB can
reduce need for blood sampling by nearly 30%. However, current devices are costly and
has a significant recurring cost of consumables such as disposable tips etc.
b. TcB can be used in infants of 35 weeks or more of gestation after 24 hr. TcB is unreliable
in infants less than 35 weeks gestation and during initial 24 hr of age. TcB has a good
correlation with TSB at lower levels, but it becomes unreliable once TSB level goes
beyond 14 mg/dL.
c. Hour specific TcB can be used for prediction of subsequent hyperbilirubinemia. TcB
value below 50th centile for age would rule out the risk of subsequent
hyperbilirubinemia with high probability (high negative predictive value)7
d. Trends in TcB values by measuring 12 hr apart would have a better predictive value than
a single value.8
e. We routinely perform TcB measurement in infants of 35 wk or more gestation to screen
for hyperbilirubinemia. A TcB value of greater than 12 to 14 mg/dL is confirmed by TSB
measurement.2. Measurement of TSB
a. Indication of TSB measurement:
i. Jaundice in first 24 hour
ii. Beyond 24 hr: if visually assessed jaundice is likely to be more than 12 to 14
mg/dL (as beyond this TSB level, visual assessment becomes unreliable) or
approaching the phototherapy range or beyond.
iii. If you are unsure about visual assessment
iv. During phototherapy, for monitoring progress and after phototherapy to check
for rebound in select cases (such as those with hemolytic jaundice)
b. Frequency of TSB measurement depends upon the underlying cause (hemolytic versus
non-hemolytic) and severity of jaundice as well as host factors such as age and
gestation. In general, in nonhemolytic jaundice in term babies with TSB levels being
below 20 to 22 mg/dL, TSB can be performed every 12 to 24 hr depending upon age of
the baby. As opposed to this, a baby with Rh isoimmunisation would require TSB
measurement every 6 to 8 hours during initial 24 to 48 hours or so.
c. Methods of TSB measurements
i. Biochemical: High performance liquid chromatography (HPLC) remains the gold
standard for estimation of TSB. However, this test is not universally available
and laboratory estimation of TSB is usually performed by Vanden Bergh
reaction. It has marked interlaboratory variability with coefficient of variation
being up to 10 to 12 percent for TSB and over 20 percent for conjugated
fraction.10
ii. Micro method for TSB estimation: It is based on spectrophotometry and
estimates TSB on a micro blood sample. It is useful in neonates, as bilirubin is
predominantly unconjugated.
Approach to a jaundiced neonate:
A step wise approach should be employed for managing jaundice in neonates (Figure 1).
All the neonates should be visually inspected for jaundice every 12 hr during initial 3 to 5 days of life.
TcB can be used as an aid for initial screening of infants. Visual assessment (when performed properly)
and TcB have reasonable sensitivity for initial assessment of jaundice.
As a first step, serious jaundice should be ruled out. Phototherapy should be initiated if the infant meets
the criteria for serious jaundice. TSB should be determined subsequently in these infants to determine
further course of action.
Though recommended by AAP5, screening of all infants with TSB in order to predict the risk of
subsequent hyperbilirubinemia does not seem to be a feasible option in resource restricted settings.Figure 1: Approach to an infant with jaundice
Perform visual assessment (VA) of jaundice: every 12 h during initial 3 to 5 days of life.
VA can be supplemented with transcutneous bilirubinometry (TcB), if available
Step 1: Does the baby have serious jaundice*?
Yes No
Start
phototherapy Step 2: Does the infant have significant jaundice to
require TSB measurement#?
Yes No
Measure TSB level and determine if baby requires Continued observation every
phototherapy or exchange transfusion (refer to Table 1) 12 to 24 hr for initial 3 to 5
days
Step 3: Determine the cause of jaundice
(Table 2) and provide supportive and
follow up care
* #
Serious jaundice: Measure serum bilirubin if:
a. Presence of visible jaundice in first 24 h a. Jaundice in first 24 hour
b. Yellow palms and soles anytime b. Beyond 24 hr: if on visual assessment or by transcutenous
c. Signs of acute bilirubin encephalopathy or kernicterus: bilirubinometry, TSB is likely to be more than 12 to 14
hypertonia, abnormal posturing such as arching, mg/dL or approaching phototherapy range or beyond.
retrocollis, opisthotonus or convulsion, fever, high c. If you are unsure about visual assessment
pitched cry)
th
d. TcB value more than 95 centile as per age specific
nomogramManagement of jaundice
1. Infants born at gestation of 35 weeks or more
American Academy of Paediatrics (AAP) criteria should be used for making decision regarding
phototherapy or exchange transfusion in these infants.5 AAP provides two age-specic
nomograms- one each for phototherapy and exchange transfusion. The nomograms have lines
for three different risk categories of neonates (Figure 2 and 3). These lines include one each for
for lower risk babies (38 wk or more and no risk factors), medium risk babies (38 wk or more
with risk factors, or 35 wk to 37 wk and without any risk factors) and higher risk (35 wk to 37 wk
and with risk factors).
TSB value is taken for decision making and direct fraction should not be reduced from it. As a
rough guide, phototherapy is initiated if TSB vales are at or higher than 10, 13, 15 and 18 mg/dL
at 24, 48, 72 and 96 hours and beyond, respectively in babies at medium risk. The babies at
lower and higher risk have their cut-offs at approximately 2 mg/dL higher or 2 mg/dL lower than
that for medium risk babies, respectively.
Risk factors include presence of isoimmune hemolytic anemia, G6PD deficiency, asphyxia,
temperature instability, hypothermia, sepsis, significant lethargy, acidosis and
hypoalbuminemia.
Figure 2. AAP nomogram for phototherapy in hospitalized infants of 35 or more weeks’ gestation.5Figure 3 depicts nomogram for exchange transfusion in three risk categories of babies. Any baby showing signs of bilirubin encephalopathy such as hypertonia, retrocollis, convulsion, fever etc should receive exchange transfusion without any delay. Figure 3. AAP nomogram for exchange transfusion in infants 35 or more weeks’ gestation.5
2. Preterm babies
There are no consensus guidelines to employ phototherapy or exchange transfusion in preterm
babies. The proposed TSB cut-offs for phototherapy and exchange transfusion are arbitrary and
clinical judgement should be exercised before making a decision (Table 1).
Table 1 Phototherapy and exchange transfusion cut-offs for preterm babies9
Total serum bilirubin (mg/dL)
Birth weight Healthy baby Sick baby
Phototherapy Exchange Phototherapy Exchange
transfusion transfusionTherapeutic options
1. Phototherapy
Phototherapy (PTx) remains the mainstay of treating hyperbilirubinemia in neonates. PTx is
highly effective and carries an excellent safety track record of over 50 years. It acts by
converting insoluble bilirubin (unconjugated) into soluble isomers that can be excreted in urine
and feces. Many review articles have provided detailed discussion on phototherapy related
issues. The bilirubin molecule isomerizes to harmless forms under blue-green light (460 to 490
nm); and the light sources having high irradiance in this particular wavelength range are more
effective than the others.
Types of phototherapy lights
The phototherapy units available in the market have a variety of light sources that include
florescent lamps of different colors (cool white, blue, green, blue-green or turquoise) and
shapes (straight or U-shaped commonly referred as compact florescent lamps ie CFL), halogen
bulbs, high intensity light emitting diodes (LED) and fibro-optic light sources.
With the easy availability and low cost in India, CFL phototherapy is being most commonly used
device. Often, CFL devices have four blue and two white (for examination purpose) CFLs but this
combination can be replaced with 6 blue CFLs in order to increase the irradiance output.
In last couple of years, blue LED is making inroads in neonatal practice and has been found to at
least equally effective. LED has advantage of long life (up to 50,000 hrs) and is capable of
delivering higher irradiance than CFL lamps.
Fiber-optic units can be used to provide undersurface phototherapy in conjugation with
overhead CFL/LED unit to enhance the efficacy of PTx but as a standalone source, fiber-optic
unit is lesser effective than CFL/LED unit.
It is important that a plastic cover or shield be placed before phototherapy lamps to avoid
accidental injury to the baby in case a lamp breaks.
Maximizing the efficacy of phototherapy
The irradiance of PTx lights should be periodically measured, and a minimum level of 30
μW/cm2/nm in the wavelength range of 460 to 490 nm must be ensured. As the irradiance
varies at different points on the footprint of a unit, it should be measured at several points. The
lamps should be changed if the lamps are flickering or ends are blackened, if irradiance falls
below the specified level or as per the recommendation of manufacturers.
Expose maximal surface area of the baby. Avoid blocking the lights by any equipment (say
radiant warmer), a large diaper or eye patch, a cap or hat, tape, dressing or electrode etc.
ensure good hydration and nutrition of the baby. Make sure that light falls on the baby
perpendicularly if the baby is in incubator. Minimize interruption of Ptx during feeding sessions
or procedures.Administering phototherapy Make sure that ambient room temperature is optimum (250 to 280) to prevent hypothermia or hyperthermia in the baby. Remove all clothes of the baby except the diaper. Cover the baby’s eyes with patches, ensuring that the patches do not block the baby’s nostrils. Place the naked baby under the lights in a cot or bassinet if weight is more than 2 kg or in an incubator or radiant warmer if the baby is small (
Table 2: Type and volume of blood for exchange transfusion
SN Condition Type of blood
1 Rh isoimmunization Rh negative and blood group ‘O’ or that of baby
Suspended in AB plasma
Cross matched with baby’s and mother’s blood
2 ABO incompatibility Rh compatible and blood group ‘O’ (Not that of baby)
Suspended in AB plasma
Cross matched with baby’s and mother’s blood
3 Other conditions (G6PD Baby’s group and Rh type
deficiency, non-hemolytic, Cross matched with baby’s and mother’s blood
other isoimmune
hemolytic jaundice
Volume of blood: Twice the blood volume of baby (total volume: 160 to 180 mL/kg)
To prepare blood for DVET, mix two thirds of packed cells and one-third of plasma
3. Intravenous immunoglobulins (IVIG)
IVIG reduces hemolysis and production of jaundice in isoimmune hemolytic anemia (Rh
isoimmunisation and ABO incompatibility) and thereby reduces the need for phototherapy and
exchange transfusion.
We give IVIG (0.5 to 1 gm/kg) in all cases of Rh isoimmunisation and selected case of ABO
incompatibility with severe hemolysis. IVIG administration can cause intestinal injury and
necrotizing enterocolitis.
4. IV hydration
Infants with severe hyperbilirubinemia and evidence of dehydration (e.g. excessive weight loss)
should be given IV hydration. An extra fluid of 50 mL/kg of N/3 saline over 8 hr decreases the
need for exchange transfusion.11
5. Other agents
There is no proven evidence of benefit of drugs like phenobarbitone, clofibrate, or steroids to
prevent or treat hyerbilirubinemia in neonates and therefore these agents should not be
employed in treatment of jaundiced infants.
Prolonged jaundice
There is no good definition of prolonged jaundice (PJ). Generally, persistence of significant jaundice for
more than 2 wk in term and more than 3 weeks in preterm babies is taken as PJ. Though, it is not
uncommon to see persistence of mild jaundice in many infants for 4 to 6 weeks of age. Most of these
babies do well without any specific intervention or investigation.The first and foremost step to manage an infant with PJ is to rule out cholestasis (Figure 2). Yellow colored urine is a reasonable marker for cholestasis; however the urine color could be normal during initial phase of cholestasis. For the practical purpose, an infant with PJ with normal colored urine can be considered to have unconjugated hyperbilirubinemia. If the infant has dark colored urine, the infant should be managed as per cholestasis guidelines. Infants with true PJ (unconjugated hyperbilirubinemia) should be assessed clinically for severity and possible cause of prolongation of jaundice (Table 3). If the clinical assessment of jaundice suggests TSB levels below phototherapy cut offs for age (say
Table 3: Causes of prolonged jaundice Common 1. Inadequacy of breastfeeding 2. Breast milk jaundice 3. Cholestasis 4. Continuing hemolysis eg Rh, ABO and G6PD hemolysis Rare 1. Extravasated blood eg cephalhematoma 2. Hypothyroidism 3. Criggler Najjar Syndrome 4. GI obstruction such as malrotation 5. Gilbert syndrome
Figure 2: Approach to a neonate with prolonged jaundice
Persistence of jaundice >2 wk in term & >3 wk in preterm babies
Check if the infant is passing high colored urine
(staining nappies)
If yes: manage as per If ‘No’:
cholestasis guidelines 1. Visually assess severity of jaundice (measure TSB, if required)
guidelines 2. Assess for and manage inadequate breastfeeding
3. Perform clinical examination to ascertain the cause:
extravasated blood, hemolysis, hypothyroidism1
Level of jaundice/TSB not in PTx range: TSB in PTx range:
Manage conservatively Initiate PTx
Follow up as needed until resolution of Perform: G6PD, thyroid screen, ABO of infant &
jaundice mother, if not done earlier
TSB persistently high, unresponsive to PTx and hovering
in exchange range: consider cessation of breastfeeding
for 48 h (required in exceptional cases only)
TSB persistent high despite PTx/cessation of
breastfeeding: consider phenobarbitone trial to rule
out CNS
1
thyroid screen can be considered at this stage
TSB: total serum bilirubin; CNS: Crigglar Najjar syndrome; PTx: phototherapyResearch issues relevant to Indian context are outlined in Table 4.
Table 4: Research issues in neonatal jaundice
S Research Subjects Study Intervention Outcomes to be
N question/ design measured
objective
s
1. What is Neonates with Randomiz Gp 1: Safety and
efficacy non-hemolytic ed trial The infant is feasibility
and jaundice (TSB discharged and outcomes: ability of
safety of well below home the family to
home exchange phototherapy is manage,
photothe transfusion provided temperature of
rapy? range) baby, family’s
Gp 2: photoherapy perceptions, any
in the hospital mishaps
Efficacy outcomes:
failure of
phototherapy,
duration of
phototherapy
2. Ability of Neonates with Diagnosti Test: visual Sensitivity;
parents jaundice (all c test in a estimation of specificity and
to severity level) cohort jaundice by the likelihood ratios
correctly parents
detect
significan Gold standard:
t jaundice visual estimation of
jaundice by the
paediatrician & TSB
3. To Neonates with Randomiz Gp 1: fibroptic failure of
compare non-hemolytic ed trial phototherapy phototherapy,
efficacy jaundice (TSB duration of
of well below Gp 2: conventional phototherapy and
fibroptic exchange Ptx rate of bilirubin
with transfusion decline
conventio range)
nal (CFL)
Ptx
4. To Neonates with Randomiz Gp 1: double failure of
compare non-hemolytic ed trial surface phototherapy,
efficacy jaundice (TSB phototherapy duration of
of . well below phototherapy and
double exchange Gp 2: single surface rate of bilirubin
surface vs transfusion Ptx decline
single range)
surface
Ptx
5. Do the Neonates with Cohort Gp 1: Neonates Duration of
babies cry non-hemolytic study with non-hemolytic phototherapy
more jaundice and jaundice
often gestation and Gp 2: Gestation and
under postnatal-age postnatal-age
photothe matched matched neonates
rapy? neonates without
without hyperbilirubinemiahyperbilirubin
emia
6. Temperat Neonates with Cohort None Measurement of
ure hyperbilirubin study ambient and baby’s
variation emia temperature every
under undergoing 2 to 4 hr
different phototherapy
Photothe with different
rapy types of
devices phototherapy
devices
(staright
lamps, CFL,
LED, halogen
lamp)
7. Efficacy Neonates with Randomiz Experiment 1 failure of
of non-hemolytic ed trial Gp 1: Intermittent phototherapy,
intermitte jaundice phototherapy (2 hr duration of
nt vs. on and 2 hr off) phototherapy and
continuo Gp 2: Continuous rate of bilirubin
us ptx phototherapy decline
without any off
period
Experiment 2
Gp 1: Continuous
phototherapy
during day time
and no
phototherapy
during night time
(2100 to 0600 hrs)
Gp 2: Continuous
phototherapy
without any off
period
8. Efficacy Neonates with Randomiz Gp 1: turquoise failure of
of blue non-hemolytic ed trial light phototherapy phototherapy,
green jaundice (TSB duration of
(turquois well below Gp 2: blue light phototherapy and
e) vs. blue exchange phototherapy rate of bilirubin
ptx transfusion decline
range)
9. Predictor Neonates with Cohort Monitor the infants
s of ABO settings study for presence and
jaundice (mother being absence of risk
in ABO ‘O’ and baby factors (
settings either ‘A’ or ‘B’
10. Single vs. Neonates with Randomiz Gp 1: PTx stopped Need for re-
two non-hemolytic ed trial when one TSB initiation of
values jaundice value is below age phototherapy
below specific cut-off Duration of
cut-offs phototherapy
for Gp 2: PTx stopped Rate of
stopping when two bilirubin
PTx consecutive TSB decline
values are belowage specific cut-off
11. What
1 is Late preterm Cohort Measure birth Follow the infants
populatio and term study weight and weight for development of
n neonates and 72 h precisely hyperbilirubinemia
attributab to calculate %
le risk of weight loss. Collect Calculate adjusted
feeding info on other risk odds ratio,
inadequa factors such as attributable risk
cy for oxytocin use, and population
hyperbilir cephalhematoma, attributable risk for
ubinemia blood group feeding inadequacy,
in incompatibility,
jaundice G6PD deficiency,
mutations,
ethnicity and
others.References
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